Synthesis And Anticonvulsant Activity Of 3-Substituent-1,3,4,5-tetrahydro-2H-benzo[b]Azepin-2-one Derivatives

Epilepsy is one of the most common diseases,It self is uncontrolled and may occur without warning on anyone's.Benzoxazepine With better drug activity,we have been modified to study anticonvulsive activity by using Benzoxazepine as a precursor compound.The predecessors of our laboratory have modified the benzene ring site of the Benzoxazepine.It is found that the compound has some anticonvulsive activity.on this basis,I have decided to modify the c-3 site of the heterocyclic ring to explore its anticonvulsive activity.These results provided helpful information for further research.We have synthesized a series of 3-(substituted amino)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one compounds(8a-e)and 3-(substituted oxy)-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one compounds(5a-i).On the product of synthesis of MS,IR and NMR structure characterization,And on the product of synthesis of MES,sc-PTZ,rotation tests such as pharmacological test.3-hydroxy-1,3,4,5-tetrahydro-2H-benzo[b]azepin-2-one has the best activity In this series of material.The median effective is 26.4 mg/kg,The median toxicity is 83.3 mg/kg,the PI is 3.2.Compound 5 of MES ED50 though higher than that of Phenytoin and Carbamazepin is far less than the numerical approach of Valproate and Phenobarbital,Close to the value of PI with existing listed drug.And compounds 5 the resistance of Sc-PTZ ED50 though higher than that of Phenobarbital,but lower than that of Valproate,Phenytoin and Carbamazepin.Compounds 5 with moderate anticonvulsants activity.